The present invention generally relates to a medical apparatus and procedure for dispensing a biologically active compound. The present invention particularly relates to a medical apparatus and procedure for dispensing a biologically active compound during a minimally invasive surgical technique, such as laparoscopic surgery.
Minimally invasive surgical techniques, such as laparoscopic surgery, typically include the use of a trocar assembly. A trocar assembly includes a trocar (sometimes referred to as an "obturator") positioned within the lumen of a cannula. The trocar and cannula are advanced through a body cavity wall so as to create a small opening or a port site wound therein. The trocar is then completely removed from the lumen of the cannula such that the cannula's lumen provides an entrance for laparoscopic instruments into the interior of the body cavity. The body cavity is then insufflated with an inert gas, such as CO.sub.2, to provide easier access to the organs contained therein. An alternative to insufflation, which also aids in intra-abdominal visualization and provides access to the organs, is a mechanical lifting device. Once the surgery is complete the cannula is completely removed from the port site wound to rapidly desufflate the body cavity.
Surgery performed by using minimally invasive techniques is generally associated with lower postoperative morbidity, slower tumor growth, shorter postoperative stay, less postoperative pain, decreased cost, and quicker recovery as compared to "open" or conventional surgical techniques.sup.(1,2,3,4,5,6). Because of the aforementioned advantages, these minimally invasive techniques are being applied to an increasing variety of all surgical procedures. For example, laparoscopic procedures for the resection of malignancies have emerged. In particular, laparoscopic colectomy for carcinoma of the colon has been developed, and it has been reported that the initial results of these procedures have advantages over operations performed in the traditional open manner.sup.(5,6,14). Moreover, it is hoped that the long term results of these procedures will be comparable, or better than, those performed in the traditional open manner.
However, the development of laparoscopic surgery for cancer has been hindered because of the major concern regarding the implantation of tumor cells in the port site wound.sup.(2,3,6,7). In fact, numerous port site recurrences have been documented in the medical literature heretofore, and these recurrences are associated with a decreased survival rate for patients who may have had a curative cancer.sup.(2,3,6,7). Specifically, the medical literature reports that the incidence of tumor cell implantation ranges from as high as 20% to as low as 0%.sup.(8). The studies generating the aforementioned data utilized highly skilled and experienced laparoscopic surgeons practicing at major university programs. However, in spite of utilizing highly skilled and experienced laparoscopic surgeons, the data indicates that the incidence of tumor cell implantation in the surgical wound is greater when employing laparoscopic techniques as compared to when conventional surgical techniques are used (i.e. 0.6% implantation incidence for conventional techniques.sup.(9) compared to 1% incidence for laparoscopic techniques.sup.(10).
Several mechanisms may be responsible for the above discussed implantation of tumor cells in the port site wound. For example, minimally invasive surgical techniques for treating cancer require the insertion and removal of laparoscopic instruments or cameras through the lumen of the cannula. In addition, these surgical techniques require that the cannula itself be moved relative to the port site wound such that the cannula is advanced further into, or withdrawn from, the body cavity.sup.(11). Moving the cannula in the above described manner facilitates a surgeon's ability to optimally locate instruments within the body cavity thereby helping to ensure the successful completion of the medical procedure. However, the aforementioned manipulations of the laparoscopic instruments and cannula may result in the exposure of the port site wound to exfoliated cancer cells which creates a risk of implanting tumor cells in the walls of the port site wound.sup.(11,12). In particular, exfoliated cancer cells may adhere to and thus contaminate a portion of the exterior surface of the cannula.sup.(11,12). The contaminated portion of the exterior surface of the cannula may then be advanced into contact with the port site wound during insertion and removal from the port site wound.sup.(11,12). This contact may dislodge the exfoliated cancer cells from the exterior surface of the cannula and thus cause the exfoliated cancer cells to be implanted in the port site wound.sup.(11,12).
Furthermore, studies have shown that a physician may undergo a significant learning curve before becoming proficient in the performance of advanced laparoscopic surgery, such as cancer surgery.sup.(3,13,16). As a result, a relatively inexperienced surgeon may have a tendency to manipulate or handle a tumor to a greater degree during a surgical procedure than an experienced surgeon. Studies have shown a 14.6% incidence of viable tumor cells in proximity of the specimen where the surgeon is working with his or her instruments.sup.(15). In addition, an inexperienced surgeon may have a tendency to insert and withdraw an instrument through the lumen of the cannula a greater number of times than an experienced surgeon. The above described increased manipulation of the instrument or the tumor can result in a greater incidence of tumor cell implantation in the port site wound.sup.(11,12).
Regardless of how these cells contaminate the wound, once implanted therein, viable tumor cells can cause a subcutaneous metastases or "port site recurrence" after the resection of malignant tissue. These "port site recurrences" have delayed the advancement of laparoscopic cancer surgery.sup.(2,6,7,8,9,10,11,12) into all fields of cancer surgery, and is one reason why the benefits of laparoscopic surgery have not been available to cancer patients.
Furthermore, laparoscopic surgery performed for general surgery, gynecological surgery, urological surgery, or any other intra-abdominal infection is associated with a small but real incidence of port site wound infection.sup.(1). The infecting bacteria causing these illnesses can contaminate the port site wound in the same manner as discussed above with regard to tumor cell contamination, and these infections can increase a patient's morbidity and consequently the length of a patient's hospital stay, thereby considerably increasing their hospital bill.
One way of addressing the problem of potential tumor or infectious cell implantation in the port site wound is to apply a biologically active compound, such as a cytotoxic agent which kills tumor or infectious cells, on a medical apparatus (e.g. a trocar assembly) utilized in the laparoscopic procedure. By placing such a compound on the medical apparatus the biologically active compound becomes disposed on the interior surface of the body cavity and on the surface of the port site wound. Having the biologically active compound disposed on the medical apparatus, the interior surface of the body cavity, and the surface of the port site wound establishes a "pharmacological barrier" which prevents any viable tumor or infectious cells from becoming implanted in the port site wound.
Heretofore, biologically active compounds were disposed on the medical apparatus by various methods. For example, dipping the medical apparatus in a solution or suspension of the biologically active compound, applying the biologically active compound to the medical apparatus with an applicator such as a cotton swab, or injecting the intraperitoneal surface with the biologically active compound.sup.(16,17). However, the aforementioned methods of administering the biologically active compound suffer from several drawbacks. For example, these methods are inconvenient, messy, inexact, or highly variable. In addition, these methods do not allow the amount of the biologically active compound administered to the patient via the medical apparatus to be appropriately controlled. Controlling the amount administered to a patient is important since it allows the physician to carefully adjust the dose of the biologically active compound and thus avoid any undesirable side effects while maximizing the delivery of the biologically active compound. In addition, controlling the dose allows the physician to collect dose response data, and thus measure the effectiveness of various pharmacological regimens. With the recent advances in the fields of biotechnology, genetic engineering, and pharmacology, there is a need to accurately, efficiently, and reproducibly deliver current and future biologically active agents during the performance of a minimally invasive surgical technique.
What is needed therefore is a medical apparatus and procedure for disposing a biologically active compound which addresses the above described drawbacks.